Monocytes and macrophages play an important role in human biology, both as a component of the hematopoietic system and within the stroma and tissue microenvironment where they contribute trophic and clearance functions. They constitute a widely dispersed cellular system throughout the body, interacting with host cells and foreign invaders through their versatile biosynthetic and secretory responses, to maintain physiologic homeostasis. They are specialized migratory or sessile phagocytes, present within the circulation and extravascular tissue compartment, contributing to diverse pathologic processes directly and through their production of bioactive products. Because of their extensive heterogeneity and plasticity, the centrality of monocytes and their progeny has not always been recognized by hematologists. The origin, life span, and functions of the monocyte are the focus of this chapter, including their relevance to health and disease in humans, based on current understanding of their properties. The relationship of monocytes and macrophages to dendritic cells, and monocyte-derived cells with a specialized immunologic role in T-lymphocyte activation, are described. Together, macrophages and dendritic cells are major antigen-presenting cells, contributing to host defense, innate and acquired immunity, and inflammation, as well as noninfectious disease processes, both within and outside the lymphohematopoietic organs.
METHODS OF MONOCYTE AND MACROPHAGE STUDY
There has been a resurgence of interest in the in situ analysis of macrophages.1 Genetic/ribonucleic acid interference manipulation, more recently with macrophage-specific/restricted promoters, has been used to knock down macrophage genes or messenger RNA, and to mark cells with fluorescent labels such as green fluorescent protein. Of particular value in tracing their origins and distribution has been the use of fractalkine receptor-transgenics,2 and myeloid-specific lysozyme-Cre for targeted ablation.3 Random chemical mutagenesis has been spectacularly successful in validating known, and discovering novel, gene targets that affect macrophage functions.4,5 A wider range of experimental models (Drosophila, zebra fish) have facilitated interspecies comparisons of macrophage migration and phagocytosis in vivo.6,7 The analysis of microRNA expression8 and functions is still in its infancy and is likely to generate important insights into monocyte/macrophage gene expression in health and disease. Combined with improved imaging methods (fluorescent, nuclear magnetic resonance imaging-based, 2-photon microscopy), new insights have been obtained regarding the dynamic behavior of macrophages and dendritic cells (DCs) in vivo.9 There has been progress in provoking embryonic and induced pluripotent stem cell differentiation into macrophages and DCs in vitro, opening the possibility of introducing mutations into human genes, to complement the naturally occurring material derived from human inborn errors and resultant genetic diseases.10
Acronyms and Abbreviations:
CR, complement receptor; DC, dendritic cell; DC-SIGN, dendritic cell–specific intercellular adhesion molecule-3–grabbing nonintegrin; EMR, epidermal growth factor module-containing mucin-like hormone receptor; FACS, fluorescence-activated cell sorting; FcR, Fc receptor; GM-CSF, granulocyte-macrophage colony-stimulating factor; IFN-γ, interferon-γ; IL, interleukin; LPS, lipopolysaccharide; M-CSF, macrophage colony-stimulating factor; MARCO, macrophage receptor with a collagenous structure; ...